Biosensors usually provide an analysis of a biological fluid, such as whole blood, urine, or saliva. Typically, a biosensor analyzes a sample of the biological fluid to determine the concentration of one or more analytes, such as glucose, uric acid, lactate, cholesterol, or bilirubin, in the biological fluid. The analysis is useful in the diagnosis and treatment of physiological abnormalities. For example, a diabetic individual may use a biosensor to determine the glucose level in blood for adjustments to diet and/or medication.
A biosensor may provide an abnormal output during the analysis of the biological fluid. The abnormal output may be in response to an error during the analysis of the biological fluid. The error may be from one or more factors such as the physical characteristics of the sample, the environmental aspects of the sample, the operating conditions of the biosensor, interfering substances, and the like. Physical characteristics of the sample include the hematocrit level and the like. Environmental aspects of the sample include temperature and the like. Operating conditions of the biosensor include underfill conditions when the sample size is not large enough, slow-filling of the sample, intermittent electrical contact between the sample and one or more electrodes in the biosensor, and the like. Interfering substances include ascorbic acid, acetaminophen, and the like. There may be other factors and/or a combination of factors that cause the error and/or abnormal output.
Biosensors may be implemented using bench-top, portable, and like devices. The portable devices may be hand-held. Biosensors may be designed to analyze one or more analytes and may use different volumes of biological fluids. Some biosensors may analyze a single drop of whole blood, such as from 0.25-15 microliters (μL) in volume. Examples of portable measuring devices include the Ascensia Breeze® and Elite® meters of Bayer Corporation; the Precision® biosensors available from Abbott in Abbott Park, Ill.; Accucheck® biosensors available from Roche in Indianapolis, Ind.; and OneTouch Ultra® biosensors available from Lifescan in Milpitas, Calif. Examples of bench-top measuring devices include the BAS 100B Analyzer available from BAS Instruments in West Lafayette, Ind.; the CH Instruments' Electrochemical Workstation available from CH Instruments in Austin, Tex.; the Cypress Electrochemical Workstation available from Cypress Systems in Lawrence, Kans.; and the EG&G Electrochemical Instrument available from Princeton Research Instruments in Princeton, N.J.
Biosensors usually measure an electrical signal to determine the analyte concentration in a sample of the biological fluid. The analyte typically undergoes an oxidation/reduction or redox reaction when an input signal is applied to the sample. An enzyme or similar species may be added to the sample to enhance the redox reaction. The input signal usually is an electrical signal, such as a current or potential. The redox reaction generates an output signal in response to the input signal. The output signal usually is an electrical signal, such as a current or potential, which may be measured and correlated with the concentration of the analyte in the biological fluid.
Many biosensors have a measuring device and a sensor strip. A sample of the biological fluid is introduced into a sample chamber in the sensor strip. The sensor strip is placed in the measuring device for analysis. The measuring device usually has electrical contacts that connect with electrical conductors in the sensor strip. The electrical conductors typically connect to working, counter, and/or other electrodes that extend into a sample chamber. The measuring device applies the input signal through the electrical contacts to the electrical conductors in the sensor strip. The electrical conductors convey the input signal through the electrodes into a sample deposited in the sample chamber. The redox reaction of the analyte generates an output signal in response to the input signal. The measuring device determines the analyte concentration in response to the output signal.
The sensor strip may include reagents that react with the analyte in the sample of biological fluid. The reagents may include an ionizing agent for facilitating the redox of the analyte, as well as mediators or other substances that assist in transferring electrons between the analyte and the conductor. The ionizing agent may be an analyte specific enzyme, such as glucose oxidase or glucose dehydrogenase, which catalyzes the oxidation of glucose in a whole blood sample. The reagents may include a binder that holds the enzyme and mediator together.
Many biosensors include one or more error detection systems to prevent or screen out analyses associated with an error. The concentration values obtained from an analysis with an error may be inaccurate. The ability to prevent or screen out these inaccurate analyses may increase the accuracy of the concentration values obtained. The error detection system may detect and compensate for an error such as a sample temperature that is different from a reference temperature. The error detection system may detect and stop the analysis of the biological fluid in response to an error such as an underfill condition.
Some biosensors have an error detection system that detects and compensates for the sample temperature. Such error detection systems typically compensate the analyte concentration for a particular reference temperature in response to the sample temperature. A number of biosensor systems compensate for temperature by changing the output signal prior to calculating the analyte concentration from a correlation equation. Other biosensor systems compensate for temperature by changing the analyte concentration calculated by the correlation equation. Biosensor systems having an error detection system for the sample temperature are described in U.S. Pat. Nos. 4,431,004; 4,750,496; 5,366,609; 5,395,504; 5,508,171; 6,391,645; and 6,576,117.
Some biosensors have an error detection system that detects whether an underfill condition exists. Such error detection systems typically prevent or screen out analyses associated with sample sizes that are of insufficient volume. A number of underfill detection systems have one or more indicator electrodes that detect the partial and/or complete filling of a sample chamber within a sensor strip. Some underfill detection systems have a third electrode in addition to counter and working electrodes used to apply an input signal to a sample of the biological fluid. Other underfill detection systems use a sub-element of the counter electrode to determine whether the sensor strip is underfilled. Biosensor systems having an error detection system for underfill conditions are described in U.S. Pat. Nos. 5,582,697 and 6,531,040.
While error detection systems balance various advantages and disadvantages, none are ideal. These systems usually are directed to detect and respond to a particular type of error. However, these systems typically do not assess or determine whether the output signal from the biosensor is a normal or abnormal response from the analysis of the biological fluid. Consequently, the biosensor may provide an inaccurate analysis when an error detection system does not detect an error. Additionally, the biosensor may provide an inaccurate analysis when an error detection system does not detect an error from a combination of factors that individually would not cause an error.
Accordingly, there is an ongoing need for improved biosensors, especially those that may provide increasingly accurate and/or precise detection of abnormal output signals from a biosensor. The systems, devices, and methods of the present invention overcome at least one of the disadvantages associated with conventional biosensors.